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Jian-Nan Liu, Zhi-Jun Yu, Li-Meng Liu, Ning-Xin Li, Rong-Rong Wang, Chun-Mian Zhang, Jing-Ze Liu
Francisella-like endosymbionts (FLEs) with significant homology to Francisella tularensis (γ-proteobacteria) have been characterized in several tick species, whereas knowledge on their distribution and population dynamics in ticks remains meager. Hence, in the current study, we identified a novel Francisella-like endosymbiont (FLEs-Hd) from the tick Haemaphysalis doenitzi and evaluated the putative functions of this symbiont. Results indicated that FLEs-Hd had 100% infection rate and a perfect vertical transmission in H...
October 12, 2016: Scientific Reports
R J Saint, R V D'Elia, C Bryant, G C Clark, H S Atkins
Francisella tularensis is a Gram-negative intracellular bacterium that causes the disease tularemia. The disease can be fatal if left untreated and there is currently no licenced vaccine available; the identification of new therapeutic targets is therefore required. Toll-like receptors represent an interesting target for therapeutic modulation due to their essential role in generating immune responses. In this study, we analysed the in vitro expression of the key mitogen-activated protein kinases (MAPKs) p38, JNK and ERK in murine alveolar macrophages during infection with F...
October 6, 2016: European Journal of Clinical Microbiology & Infectious Diseases
Kristen M Holland, Sarah J Rosa, Karsten R O Hazlett
One of the hallmarks of pulmonary tularemia, which results from inhalation of Francisella tularensis - a significant bioterrorism concern, is the lack of an acute TH1-biased inflammatory response in the early phase of disease (days 1-3) despite significant bacterial loads. In an effort to understand this apparent hypo-responsiveness, many laboratories have utilized in vitro cell-based models as tools to probe the nature and consequences of host cell interactions with F. tularensis. The first uses of this model suggested that mammalian host cells recognize this bacterium principally through TLR2 to evoke a robust, classical TH1-biased cytokine response including TNF, IL-6, IL-1β, and IFN-γ...
June 2016: Journal of Bioterrorism & Biodefense
Si Ming Man, Rajendra Karki, Miwa Sasai, David E Place, Sannula Kesavardhana, Jamshid Temirov, Sharon Frase, Qifan Zhu, R K Subbarao Malireddi, Teneema Kuriakose, Jennifer L Peters, Geoffrey Neale, Scott A Brown, Masahiro Yamamoto, Thirumala-Devi Kanneganti
The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria...
October 6, 2016: Cell
Charlotte A Hall, Helen C Flick-Smith, Sarah V Harding, Helen S Atkins, Richard W Titball
Bioluminescence imaging (BLI) enables real-time, non-invasive tracking of infection in vivo and longitudinal infection studies. In this study, a bioluminescent F. tularensis SCHU S4-lux strain was used to develop an inhalational infection model in BALB/c mice. Mice were infected intranasally and the progression of infection was monitored in real time using BLI. A bioluminescent signal was detectable from 3 days post-infection (dpi), initially in the spleen, then in the liver and lymph nodes before finally becoming systemic...
September 26, 2016: Antimicrobial Agents and Chemotherapy
G B N Assis, T F de Oliveira, I A Gardner, H C P Figueiredo, C A G Leal
Despite the worldwide occurrence of Francisella noatunensis subsp. orientalis (Fno) infection in farmed tilapia, sensitivity and specificity estimates of commonly used diagnostic tests have not been reported. This study aimed to estimate the sensitivity and specificity of bacteriological culture and qPCR to detect Fno infection. We tested 559 fish, sampled from four farms with different epidemiological scenarios: (i) healthy fish in a hatchery free of Fno; (ii) targeted sampling of diseased fish with suggestive external clinical signs of francisellosis during an outbreak; (iii) convenience sampling of diseased and clinically healthy fish during an outbreak; and (iv) sampling of healthy fish in a cage farm without a history of outbreaks, but with francisellosis reported in other farms in the same reservoir...
September 27, 2016: Journal of Fish Diseases
Crystal J Jaing, Kevin S McLoughlin, James B Thissen, Adam Zemla, Shea N Gardner, Lisa M Vergez, Feliza Bourguet, Shalini Mabery, Viacheslav Y Fofanov, Heather Koshinsky, Paul J Jackson
Francisella tularensis is classified as a Class A bioterrorism agent by the U.S. government due to its high virulence and the ease with which it can be spread as an aerosol. It is a facultative intracellular pathogen and the causative agent of tularemia. Ciprofloxacin (Cipro) is a broad spectrum antibiotic effective against Gram-positive and Gram-negative bacteria. Increased Cipro resistance in pathogenic microbes is of serious concern when considering options for medical treatment of bacterial infections. Identification of genes and loci that are associated with Ciprofloxacin resistance will help advance the understanding of resistance mechanisms and may, in the future, provide better treatment options for patients...
2016: PloS One
E Lewisch, S Menanteau-Ledouble, A Tichy, M El-Matbouli
Francisellosis, an emerging disease in many fish species, can cause high mortality in affected populations. Here we investigated the susceptibility of common carp Cyprinus carpio and sunfish Lepomis gibbosus to Francisella noatunensis subsp. orientalis (Fno), and possible transmission of the bacteria between the 2 fish species. In a challenge experiment, 3 groups of each species were injected intraperitoneally (IP) with 3 different doses of an Fno strain no. 9449 of the Norwegian Veterinary Institute, recovered from naturally infected ornamental Malawi cichlids...
September 26, 2016: Diseases of Aquatic Organisms
Kathrine R Bakkemo, Helene Mikkelsen, Audny Johansen, Børre Robertsen, Marit Seppola
Systemic infection caused by the facultative intracellular bacterium Francisella noatunensis subsp. noatunensis remains a disease threat to Atlantic cod Gadus morhua L. Future prophylactics could benefit from better knowledge on how the bacterium invades, survives and establishes infection in its host cells. Here, facilitated by the use of a gentamicin protection assay, this was studied in primary monocyte/macrophage cultures and an epithelial-like cell line derived from Atlantic cod larvae (ACL cells). The results showed that F...
September 26, 2016: Diseases of Aquatic Organisms
Alison J Scott, Bryn Flinders, Joanna Cappell, Tao Liang, Rebecca S Pelc, Bao Tran, David P A Kilgour, Ron M A Heeren, David R Goodlett, Robert K Ernst
The discovery of novel pathogenic mechanisms engaged during bacterial infections requires the evolution of advanced techniques. Here, we evaluate the dual polarity matrix norharmane (NRM) to improve detection of bacterial lipid A (endotoxin), from host and vector tissues infected with Francisella novicida (Fn). We evaluated NRM for improved detection and characterization of a wide range of lipids in both positive and negative polarities, including lipid A and phospholipids across a range of matrix assisted laser desorption-ionization (MALDI)-coupled applications...
September 19, 2016: Pathogens and Disease
Jonathan G Gerhart, Abraham S Moses, Rahul Raghavan
Ticks (order Ixodida) vector pathogenic bacteria that cause diseases in humans and other mammals. They also contain bacteria that are closely related to pathogens but function as endosymbionts that provide nutrients that are missing from mammalian blood-their sole food source. For instance, mammalian pathogens such as Coxiella burnetii and Francisella tularensis, as well as Coxiella-like and Francisella-like endosymbionts (CLEs and FLEs, respectively) occur in ticks worldwide. However, it is not clear whether the pathogens evolved from symbionts or symbionts from pathogens...
2016: Scientific Reports
Anju Singh, Tabassum Rahman, Rose Bartiss, Alireza Arabshahi, Jeevan Prasain, Stephen Barnes, Florin Marcel Musteata, Timothy J Sellati
Respiratory infection with Francisella tularensis (Ft) is characterized by a muted, acute host response, followed by sepsis-like syndrome that results in death. Infection with Ft establishes a principally anti-inflammatory environment that subverts host-cell death programs to facilitate pathogen replication. Although the role of cytokines has been explored extensively, the role of eicosanoids in tularemia pathogenesis is not fully understood. Given that lipoxin A4 (LXA4) has anti-inflammatory properties, we investigated whether this lipid mediator affects host responses manifested early during infection...
September 14, 2016: Journal of Leukocyte Biology
Lorraine Michelet, Guy Joncour, Elodie Devillers, Alessandra Torina, Muriel Vayssier-Taussat, Sarah I Bonnet, Sara Moutailler
Insular environments provide ideal natural conditions to study disease ecology, especially emerging diseases, due to clear differentiation between local and long-distance transmission. Such environments are of particular interest regarding tick-borne pathogens (TBP), since animal exchange with the mainland (along with any ticks they carry) is limited, and because such locations could lie on migratory routes for birds carrying ticks. Therefore both tick species and TBP may display different prevalence than those observed on the continent...
October 2016: Ticks and Tick-borne Diseases
Michael A Makara, Ky V Hoang, Latha P Ganesan, Elliot D Crouser, John S Gunn, Joanne Turner, Larry S Schlesinger, Peter J Mohler, Murugesan V S Rajaram
BACKGROUND: Sepsis patients with cardiac dysfunction have significantly higher mortality. Although several pathways are associated with myocardial damage in sepsis, the precise cause(s) remains unclear and treatment options are limited. This study was designed to develop a new model to investigate the early events of cardiac damage during sepsis progression. METHODS AND RESULTS: Francisella tularensis subspecies novicida (Ft.n) is a Gram-negative intracellular pathogen causing severe sepsis syndrome in mice...
September 2016: Journal of the American Heart Association
Jason G Glanzer, Jennifer L Endres, Brendan M Byrne, Shengqin Liu, Kenneth W Bayles, Greg G Oakley
OBJECTIVES: The increasing threat of drug-resistant bacteria establishes a continuing need for the development of new strategies to fight infection. We examine the inhibition of the essential single-stranded DNA-binding proteins (SSBs) SSBA and SSBB as a potential antimicrobial therapy due to their importance in DNA replication, activating the SOS response and promoting competence-based mechanisms of resistance by incorporating new DNA. METHODS: Purified recombinant SSBs from Gram-positive (Staphylococcus aureus and Bacillus anthracis) and Gram-negative (Escherichia coli and Francisella tularensis) bacteria were assessed in a high-throughput screen for inhibition of duplex DNA unwinding by small molecule inhibitors...
September 8, 2016: Journal of Antimicrobial Chemotherapy
Mélanie Rigard, Jeanette E Bröms, Amandine Mosnier, Maggy Hologne, Amandine Martin, Lena Lindgren, Claire Punginelli, Claire Lays, Olivier Walker, Alain Charbit, Philippe Telouk, Wayne Conlan, Laurent Terradot, Anders Sjöstedt, Thomas Henry
The virulence of Francisella tularensis, the etiological agent of tularemia, relies on an atypical type VI secretion system (T6SS) encoded by a genomic island termed the Francisella Pathogenicity Island (FPI). While the importance of the FPI in F. tularensis virulence is clearly established, the precise role of most of the FPI-encoded proteins remains to be deciphered. In this study, using highly virulent F. tularensis strains and the closely related species F. novicida, IglG was characterized as a protein featuring a unique α-helical N-terminal extension and a domain of unknown function (DUF4280), present in more than 250 bacterial species...
September 2016: PLoS Pathogens
Céline Terrada, Said Azza, Bahram Bodaghi, Phuc Le Hoang, Michel Drancourt
BACKGROUND: Literature reports on ophthalmological manifestations related to tularemia, a zoonose caused by the bacterium Francisella tularensis, largely refer to Parinaud's oculoglandular syndrome, which consists of the association of conjunctivitis with preauricular lymphadenitis. In this paper, we report a case of intraocular inflammation during tularemia infection. CASE PRESENTATION: A 52-year-old Caucasian man was diagnosed with unilateral uveitis. The uveitis was posterior, with a 2+ vitritis and a large yellowish lesion involving the macula with an overlying sub-retinal detachment, extending inferiorly, and subretinal hemorrhages...
2016: BMC Ophthalmology
Sung Hwan Yoon, Tao Liang, Thomas Schneider, Benjamin L Oyler, Courtney E Chandler, Robert K Ernst, Gloria S Yen, Yue Huang, Erik Nilsson, David R Goodlett
RATIONALE: Surface acoustic wave nebulization (SAWN) is an easy to use sample transfer method for rapid mass spectrometric analysis. A new standing wave (SW) SAWN chip, with higher ionization efficiency than our previously reported design, is used for rapid analysis of lipids. METHODS: The crude, yet fast, Caroff protocol was used for lipid A extraction from Francisella novicida. SW-SAWN with a Waters Synapt G2S Q-TOF mass spectrometer was used to generate lipid A ions...
August 31, 2016: Rapid Communications in Mass Spectrometry: RCM
Qingmei Jia, Richard Bowen, Bai-Yu Lee, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A safer and more effective vaccine than the unlicensed Francisella tularensis Live Vaccine Strain (LVS) is needed to protect against the biowarfare agent F. tularensis. Previously, we developed an LVS ΔcapB mutant that is significantly safer than LVS and provides potent protective immunity against F. tularensis respiratory challenge when administered intranasally but limited protection when administered intradermally unless as part of a prime-boost vaccination strategy. To improve the immunogenicity and efficacy of LVS ΔcapB, we developed recombinant LVS ΔcapB (rLVS ΔcapB) strains overexpressing various F...
September 22, 2016: Vaccine
Olle M de Bruin, H C Birnboim
BACKGROUND: DNA-based testing is becoming the preferred method both for identifying microorganisms and for characterizing microbial communities. However, no single DNA extraction method exists that is suitable for all types of microorganisms because bacteria are variable in their susceptibility to lysis by available extraction procedures. To develop and test new DNA extraction procedures, it would be helpful to determine their efficiencies. While the amount of extracted DNA can readily be measured by different methods, calculation of true efficiency requires knowledge of the initial amount of DNA in the starting bacterial sample, which cannot be done with precision by any existing method...
2016: BMC Microbiology
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